Journal of Asthma and Allergy
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Open Access Full Text Article
Approaches to the assessment of severe asthma:
barriers and strategies
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Eleanor C Majellano 1,2
Vanessa L Clark 1,2
Natasha A Winter 1,3
Peter G Gibson 1,4
Vanessa M McDonald 1,2,4
1
Faculty of Health and Medicine, National
For personal use only.
Health and Medical Research Council
Centre for Research Excellence in Severe
Asthma and the Priority Research Centre
for Healthy Lungs, The University of
Newcastle, Newcastle, NSW, Australia;
2
Faculty of Health and Medicine, School
of Nursing and Midwifery, The University
of Newcastle, Newcastle, NSW,
Australia; 3Faculty of Health and
Medicine, School of Medicine and Public
Health, The University of Newcastle,
Newcastle, NSW, Australia; 4Department
of Respiratory and Sleep Medicine, John
Hunter Hospital, Hunter Medical
Research Institute, Newcastle, NSW,
Australia
Correspondence: Vanessa M McDonald
Level 2 West Wing, Hunter Medical
Research Institute, Locked Bag 1000,
New Lambton Heights, NSW 2305,
Australia
Tel +61 24 042 0146
Fax +61 4 042 0046
Email Vanessa.McDonald@newcastle.edu.au
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This article was published in the following Dove Press journal:
Journal of Asthma and Allergy
Abstract: Asthma is a chronic condition with great variability. It is characterized by
intermittent episodes of wheeze, cough, chest tightness, dyspnea and backed by variable
airflow limitation, airway inflammation and airway hyper-responsiveness. Asthma severity
varies uniquely between individuals and may change over time. Stratification of asthma
severity is an integral part of asthma management linking appropriate treatment to establish
asthma control. Precision assessment of severe asthma is crucial for monitoring the health of
people with this disease. The literature suggests multiple factors that impede the assessment
of severe asthma, these can be grouped into health care professional, patient and organiza-
tional related barriers. These barriers do not exist in isolation but interact and influence one
another. Recognition of these barriers is necessary to promote precision in the assessment
and management of severe asthma in the era of targeted therapy. In this review, we discuss
the current knowledge of the barriers that impede assessment in severe asthma and recom-
mend potential strategies for overcoming these barriers. We highlight the relevance of
multidimensional assessment as an ideal approach to the assessment and management of
severe asthma.
Keywords: asthma, severe asthma, severity, assessment, barriers, strategies
Introduction
Asthma is a significant public health threat, affecting more than 300 million
individuals globally.1 Asthma is classified as a non-communicable disease and
leads to reduced quality of life,2 poor physical functioning3 and reduced emotional
well-being.4 The impact of this disease can be widespread and extends beyond the
person living with the disease, affecting the lives of their family members, carers,
communities and the health care system.5
Asthma is a variable chronic respiratory condition. It is characterized by symp-
toms of wheeze, cough, chest tightness, dyspnea and backed by variable airflow
limitation, airway inflammation and airway hyper-responsiveness (AHR).1 The
severity of asthma varies considerably, both between individuals and within indi-
viduals over time.1 Some people may have intermittent asthma and others may
experience severe, potentially life-threatening disease. In mild-to-moderate asthma,
inhaled corticosteroids (ICS), bronchodilators and self-management education are
the cornerstone of effective treatment.5 However, 3%6 to 10%7 of the patients
experience a severe form of asthma that fails to respond to standard therapy despite
receiving maximal treatment. Thus, severe asthma is defined as “asthma which
requires maximum controller therapy to prevent a patient from becoming
Journal of Asthma and Allergy 2019:12 235–251 235
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 Majellano et al
uncontrolled or which, despite high dose therapy remains
uncontrolled.”7 Patients diagnosed with severe asthma
endure significant difficulties in daily living, a decrease
in physical activity,3 work capacity or productivity8 and
social exclusion.2 Furthermore, patients with severe
asthma are faced with an increased comorbidity burden.2,7
There is a wide array of comorbidities present in severe
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asthma that may contribute to disease severity, mimic
asthma symptoms, and therefore confound assessment
and treatment.9 For example, chronic rhinosinusitis is a
prevalent comorbidity of asthma and contributes to disease
severity.7 Similarly, obstructive sleep apnea, obesity and
psychological factors often co-exist and complicate
management.7 These comorbidities mimic asthma symp-
toms and affect the intensity of the disease, management
or diagnosis, leading to a much greater risk of asthma
morbidity and mortality.7 Given the complexity and het-
erogeneity of the disease, assessment and management of
For personal use only.
severe asthma warrants advanced approaches.5,10
Guidelines for asthma management have proposed that
evaluation of disease severity is necessary to initialize
therapy and maintain treatment through a step-wise
process.11 Misclassification of the levels of severity may
contribute to the underuse or overuse of anti-inflammatory
medications, resulting in either poor asthma control or
adverse side-effects associated with overtreatment.11
With the advent of biological therapies,12 recognition of
the level of asthma severity is imperative to facilitate
treatment interventions to the right patients.12
The literature on diagnosing, treating and managing
severe asthma indicates that significant barriers exist
across health care settings and that these barriers relate
to health care providers, patients and organizational
systems.10 Overcoming these barriers is necessary in
order to facilitate effective assessment and accelerate
appropriate treatment for severe asthma patients.13
Therefore, identification of the barriers related to precision
assessment of severe asthma is an important step. The
purpose of this review is to discuss current knowledge of
the barriers that impede assessment in severe asthma and
to recommend potential strategies for overcoming these
barriers. We highlight the importance of multidimensional
assessment as an approach to the assessment and manage-
ment of severe asthma.
Search strategy
The literature search is current as of March 2019 using the
electronic databases CINAHL, Pub Med, Web of Science,
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Google Scholar, Wiley, and Medline. The search strategy
includes the keywords of asthma, severe asthma, severity,
assessment, barriers and strategies. English written articles
between 2014 and 2019 were retrieved and included to
reflect the current literature. However, we did not exclude
seminal papers which were highly cited and judged to be
relevant to answer our aims. We also checked reference
lists to identify relevant studies significant for our review.
Measurement of asthma severity
Severity-based stratification of patients with asthma is an
integral part of management, providing a useful blueprint
for treatment decision making.11 Categorization of asthma
severity reinforces the regulation, duration and calculation
of the amount and type of therapy to establish asthma
control.11 Patients with well-controlled asthma have mini-
mal symptoms or functional impairment related to their
disease.11
The general definition of severity implies “the intrin-
sic intensity of the disease process,”11 however, defining
severity is often challenging because asthma is associated
with a wide range of heterogeneity.14 In addition, genes
and environmental exposures like allergens, cigarette
smoke or air pollution play a crucial role that may change
or influence disease progression over time.14 Therefore,
periodic assessment is necessary to assist asthma man-
agement and treatment. To date, there is no gold standard
for classifying asthma severity or robust data showing
significant changes in disease severity in a longitudinal
cohort.15 The Global Initiative for Asthma (GINA) strat-
egy recommends that asthma severity should be deter-
mined according to the level of treatment required to
control and reduce symptoms and exacerbations.1 A
step-wise approach to treatment is recommended where
each of the five steps constitutes five levels of increasing
treatment recommended according to severity. Step 1 to 3
represents mild–moderate disease, with steps 4 and 5
depicting moderate-severe asthma, which requires high-
dose ICS/Long-Acting Beta-Agonist (LABA) treatment
to achieve and maintain asthma control.1 In some cases,
severe asthma may remain uncontrolled despite high-
dose therapy, suggesting the need for further multidimen-
sional and systematic assessment and treatment
(Figure 1).
Severe asthma assessment
The assessment of severe asthma is complex. This is because
the disease is heterogeneous in nature and associated with
Journal of Asthma and Allergy 2019:12
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Diagnosis confirmed?
Is it severe?
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Poor control
Airflow obstruction
Frequent exacorbations
Life-threatening episodes
Figure 1 Checklist for the multidimensional assessment of severe asthma.
Note: Figure reproduced with permission from the Centre of Excellence in Severe Asthma, originally developed as part of the Severe Asthma Toolkit © (http://www.
severeasthma.org.au).30
For personal use only.
many comorbidities; therefore, a multidimensional evaluation
is essential.16 Figure 1 shows a practical guide designed to
critically diagnose, characterize and manage severe asthma.
We elaborate on these steps further in the next section.
Diagnosis confirmed
Harm from asthma medications may arise from
misdiagnosis.15,17 Hence, a comprehensive work-up is
important to ascertain whether the patient has severe
asthma.9 A detailed history is the first step to the assess-
ment and diagnosis.9 The medical history should focus on
characterizing the specific symptoms, their frequency and
severity.7 Clarification of the onset of symptoms, determi-
nation of the severity of exacerbations and associated
comorbidities are also essentials.9 Accordingly, clinical
questionnaires can facilitate these assessments.9 Physical
examination of the cardio-respiratory system is also
important.9 When critical information of the patient’s
symptoms is gathered, clinicians gain a better understand-
ing of the patient’s problem.
Assessment of lung function
There are a number of standard assessments included in
lung function examinations in asthma. These include, but
are not limited to, the measurement of airflow limitation
through spirometry, assessment of bronchodilator respon-
siveness and assessment of AHR. Table 1 shows a sum-
mary of the lung function and volume assessments to
consider in severe asthma.
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Majellano et al
Individualised management plan
Is treatment optimised?
Multidimensional
High-dose ICS &
assessment
LABA or other controller
or Optimise self management skills
Moderate dose ICS & >1
Identify & manage triggers
controller
Identify & manage comorbidities
Phenotyping
Social & environmental
Inflammatory biomarkers
Biomarkers are observable characteristics that are objectively
measured as an indicator of normal or abnormal biologic
processes.28 The clinical utility of biomarkers includes four
main roles: 1) diagnosis, 2) disease staging, 3) ongoing assess-
ment of disease progression and 4) assessment of treatment
response.29 In addition to being a guide for clinicians, the
process of biomarker investigation allows for a comprehensive
understanding of the underlying molecular pathways behind
disease pathogenesis as well as the discovery of new targets
for novel therapies.29 At present, airway inflammatory bio-
markers used in practice include serum immunoglobulin-E
(IgE), peripheral blood eosinophils, sputum eosinophil counts
and exhaled fraction of nitric oxide (FeNO).29 However, lim-
itations of biomarkers do exist, impeding implementation in
clinical practice. Barriers and strategies to overcome these
limitations will be discussed in the sections below.
Is it severe?
If a diagnosis of asthma is confirmed and control has not
been achieved, asking the question of whether it is actually
severe asthma is required.9 Common features of uncon-
trolled asthma are presented in Table 2. Differentiating
between difficult to treat asthma and severe treatment
refractory asthma at this stage is integral. Key differences
between these forms of asthma are highlighted in Table 3
and differentiation can be achieved by an assessment of
asthma self-management skills, comorbidities, risk factors
and triggers, and whether treatment is indeed optimized
(Figure 1).
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Table 1 Pulmonary function tests to consider in severe asthma

Assessment Rationale Outcome Advantages Disadvantages

Lung function

Spirometry An objective test that measures the Confirms airflow Reproducible.18 Spirometers may not be readily
18 18
air that is expired and inspired. limitation. Non-invasive.18 accessible in some health care
Determines the settings.19
reversibility of airflow Caution is needed in interpreting
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limitation after the results as bronchodilator

administration of short- reversibility lacks sensitivity.18
acting bronchodilator Training and equipment costs.18
18
drug.

Airway hyper- Direct Stimuli: Methacholine. Defines the presences and Reproducible.21 Requires technical expertise.20
responsiveness Challenge or Indirect Stimuli: degree of AHR.20 Safe.21
(AHR) Hypertonic Saline/Mannitol is
utilized to determine the presence
of AHR and aid in the clinical
diagnosis.20

Exhaled nitric A surrogate marker of Type 2 airway Determines the presence Easy to Unreliable in current smokers and
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oxide inflammation. of Type 2 inflammation.22 perform lacks sufficient sensitivity and

measurements Can be used to measure compared to specificity to measure asthma
adherence.22 induced control. Readings are influenced by
sputum ICS or oral corticosteroid
analysis.22 therapy.23
Convenient Single breath technique is not
and portable.22 feasible in preschool children.23
Highly
reproducible.22
Cost
effective.22
Non-invasive.23

Lung volume An accurate and well-established Confirms the presence of Non-invasive.25 Requires technical expertise.25
assessment method to determine the total lung restrictive lung disease.24 Reproducible.25 Equipment is heavy and space
capacity.24 Confirms the presence of demanding.25
24
hyperinflation. Expensive.25
Not ideal for patients with
claustrophobia or
skeletal abnormalities.25
Overestimate lung volumes in
patients with obstruction.25

Carbon Measures the ability of the lungs to Diagnoses emphysema.27 Non-invasive.26 Results are sensitive to errors due
monoxide transfer gas and evaluates issues with Reproducible.27 to physiologic variation, test
diffusion gas transfer.26 technique, errors in gas analysis and
capacity computation algorithms.26
Abbreviations: AHR, airway hyper-responsiveness; FeNO, exhaled fraction of nitric oxide; ICS, inhaled corticosteroids.

The most common asthma management skills, comor- Is treatment optimized?

bidities, triggers and risk factors in severe asthma are shown It is essential to determine whether patients with uncon-
in Table 4.30 A careful assessment for each of these factors trolled asthma are receiving adequate treatment9 with
promotes optimal asthma control, therefore should be prior- high-doses of ICS and LABA or moderate dose ICS and
ity during clinic visits both in primary and specialist care.17 two or more controllers. A trial of add-on therapies like

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Table 2 Criteria for uncontrolled asthma Table 4 Checklist of important contributory factors in severe
asthma
Poor symptom Consistent ACQ score of >1.5, ACT score
control of <20, classified as “not well controlled.”7 Panel Assessment
Frequent severe Requiring two or more bursts of systemic
Self-management Optimal inhaler technique
exacerbations corticosteroids in the previous year (>3
7 skills Minimization of inhaler device polypharmacy
days each).
Self-monitoring of symptoms or peak flow
Serious At least one hospitalization, life-threatening
monitoring
exacerbations episode or the need for mechanical
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Adherence
ventilation in the preceding year.7
Written action plan
Airflow limitation Following applicable bronchodilator
Disease knowledge
withhold (FEV1<80% predicted (in the
presence of reduced FEV1/FVC) defined as Comorbidities Pulmonary or airway assessments:
less than lower limit of normal.7 Allergic & non-allergic rhinitis
Abbreviations: ACQ, Asthma Control Questionnaire; ACT, asthma control test; Chronic rhinosinusitis
FEV1, forced expiratory volume in one second; FVC, forced vital capacity. Dysfunctional breathing
Vocal cord dysfunction
Chronic obstructive pulmonary disease
Table 3 Asthma definitions and characteristics
Bronchiectasis
Under- Difficult-to- Severe Obstructive sleep apnea
treated treat treatment- Extrapulmonary
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asthma asthma refractory Obesity

asthma Anxiety & depression
Gastro-esophageal reflux disease (GORD)
Symptoms ++ ++ ++
Osteoporosis
Medication: _ + + Cardiovascular disease & metabolic disease
prescribed
Triggers Allergens
adequate ICS
Cigarette smoke
Asthma skills May be May be Optimized Respiratory viral infection
suboptimal suboptimal Emotional stress
Mould or dampness
Comorbidity Not managed Managed
Medications
Recommended ICS ± ICS ± LABA Phenotype and use Patient-reported triggers
management LABA Optimize of targeted therapy
Risk factors Smoking
skills and in addition to ICS/
Physical inactivity
manage LABA
Poor nutrition leading to obesity
comorbidities Optimize skills and
Poor self-management skills
manage
comorbidities
Note: Table has been reproduced with permission from John Wiley & Sons,
McDonald VM, Maltby S, Reddel HK, et al. Severe asthma: current management,
targeted therapies and future directions-Aroundtable report. Respirology. 2017;22 control.32 In severe asthma, adherence to treatment tends
(1):53–60.10
Abbreviations: ICS, inhaled corticosteroids; LABA, long-acting beta agonist; -, to be poor in both adults and children with prevalence
absent; +, present. estimated to be >50%.7 If left unaddressed, the conse-
quences of non-adherence will lead to a greater risk of
tiotropium, anti-fungal agents, montelukast and low dose asthma exacerbations and increased health care costs.33
macrolide antibiotics is often warranted before initiation of Ultimately, non-adherence may in turn lead to unnecessary
biological therapies.31 However, if benefit of these thera- treatment escalation, which can be both harmful and
pies is not achieved, appropriate treatment re-evaluation is expensive.33 Adherence to medications and inhaler tech-
required. Apart from assessing asthma treatment, adher- nique should be regularly assessed.32 Objective assessment
ence and inhaler technique should also be evaluated.32 should also be considered whenever possible (Table 5).17
Suboptimal adherence and inhalation technique are two Integrating the results of these tests identifies factors that
of the most prevalent factors resulting in poor asthma impede medication adherence.

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Table 5 Useful tools for assessing adherence
Assessment Tool
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Canister weighing
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Dose counter
Electronic inhaler
monitoring
FeNO suppression test
Serum prednisolone/
cortisol
Prescription/pharmacy
records
Abbreviations: pMDI, pressurized metered dose inhaler; FeNO, exhaled fraction of nitric oxide.
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Majellano et al
Description Advantage Disadvantage
An objective method to assess the number of doses remaining in a A reproducible technique that can assess patient adherence to Can overestimate adherence.36
34 34,35
pressurized metered dose inhaler (pMDI). medication based on the accurate weight of the canister. Cannot reveal full patterns of
medication used over time.36
Can be confounded by test
doses or dumping.36
A dose counter counts the number of doses in the inhaler to determine Improves the tracking of adherence to treatment and Can be confounded by test
the remaining amount of medication.35 increases patients’ awareness of remaining doses.34,35 doses or
dumping.36
An electronic device used to accurately assess and record adherence to Unique features include audio-visual reminders, date and Expensive.36
37 37
inhaled therapies. time tracker of each actuation of the inhaler device. Subject to mechanical failures.38
Benefits clinician in distinguishing poor treatment Self-monitoring could alter
response.37 patients’ behaviour (Hawthorne
Effect).36
An objective method to distinguish non-adherence to ICS.35 Non-invasive.35 Limited to patients with elevated
FeNO testing after directly observed inhaled corticosteroid treatment. Correlates with Type 2 inflammation.35 baseline FeNO.35
This facilitates stratification of non-adherent patients with difficult Feasible.39 Devices not available in all clinics.10
39
asthma.
A direct serum prednisolone or cortisol evaluation can be performed on Provides direct measurement of non-adherence to Requires specialized
patients taking prescribed prednisolone.40 prednisolone through prednisolone or equipment.40
Lower level indicates low adherence with oral prednisolone or poor cortisol assay.40 Expensive.40
absorption.40 Reproducible.40
Objective method to compare the dispensing ratio of preventer Simple and economical way of obtaining patients’ medication Does not provide direct
medication to reliever medication.40,41 information.35 measures of medication
Dispensing record showing large amounts of reliever medication adherence.35
indicates poor asthma control.35,40,41 No assurance that the dispensed
medication is actually taken.17
Prescription records may not be
available in all health care
settings.17
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y
dit
rbi
mo
Co
Difficult
to
treat asthma
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Figure 2 Clinical domains in the phenotyping of severe refractory asthma.
Note: Figure reproduced with permission from the Centre of Excellence in Severe Asthma, originally developed as part of the Severe Asthma Toolkit © (http://www.
severeasthma.org.au).30
Multidimensional assessment
Diagnosis and management of severe asthma offer unique
challenges because of the heterogeneity of the disease
itself. The current guidelines7 recommend that people
with severe asthma undergo a systematic assessment or
multidimensional assessment. The multidimensional
assessment includes a series of coordinated steps designed
to assist in confirming the diagnosis, recognition and treat-
ment of common comorbid conditions, and in determining
risk-factors.42 Multidimensional assessment may cover
domains related to pulmonary or airway assessments, extra-
pulmonary or comorbidity assessments as well as risk-factor
and behavioral assessments (Figure 2).16,43,44 The results
from a multidimensional assessment can be used to inform
management decisions comprising identification of thera-
peutic strategies and specialist referrals.16,43,44
To demonstrate the possible benefits of multidimen-
sional assessment, a meta-analysis of three observational
studies has reported improvements in health-related qual-
ity of life (HRQoL), asthma control and reduction in
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Majellano et al
Severe
refractory
asthma
Ai
rw
ay
s
Risk factors
exacerbations, up to a year after the implementation of
multidimensional assessment.43 More recently, McDonald
and colleagues completed the first randomized controlled
trial (RCT) in severe asthma utilizing multidimensional
assessment and individualized management targeting the
traits identified in each individual and demonstrated
improved outcomes for patients.45
Individualized management plan
Patients with severe asthma require tailored evidence-
based interventions to meet their needs. Case-management
is one approach that can assess, plan, facilitate and coor-
dinate health care delivery through partnerships with clin-
icians, patients and their families.46 In a study of older
patients with asthma and COPD, significant improvements
in quality of life were sustained for 1 year in COPD
patients who underwent multidimensional assessment and
individualized management.47 More recently, this
approach has been tested in patients with severe asthma
as described earlier.45
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Figure 3 Barriers to assessment of severe asthma by stakeholders.
Barriers to severe asthma
assessment
Precise assessment of asthma severity is key to optimizing
health and well-being of people with asthma.15 We have
described severe asthma assessment in terms of objective
tests used in diagnosis. However, it is recognized that there
are barriers to undertaking a complete and comprehensive
assessment of severe asthma in clinical practice.10 The
barriers are multifactorial and relate to system challenges,
health care professional (HCP) and patient barriers.13,32
Figure 3 summarizes the factors that influence the assess-
ment of severe asthma.
Barriers related to health care
practitioners (HCP)
A number of barriers that relate to HCPs have been iden-
tified (Figure 3). These include a lack of knowledge about
guideline-recommended therapies, inconsistent diagnosis
and management, referral pathway issues and communica-
tion gaps.10,13,32
The role of guidelines and checklists
Although evidence suggests that the use of clinical guide-
lines and checklists are beneficial and are prime
components in asthma management, unfortunately there
is also evidence showing HCPs’ low adherence to
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guidelines.32,48,49 Findings from a national survey of
severe asthma experts in Australia report that 60% of the
clinicians managing patients with severe asthma do not use
checklists, but believed they would find one useful.10 In an
observational study that assessed the barriers to improving
the management of patients with severe asthma, the under-
use of guidelines suggested suboptimal asthma control.48
There are several proposed reasons as to why HCP
adherence to guidelines and checklists may be
suboptimal.50 These include professional issues relating
to clarity of roles,51 lack of familiarity with guidelines,15,52
lack of training and skills,53 distrust about guidelines in
general,54 complex and lengthy guidelines,55 poor team-
work, lack of self-efficacy,51 poor communication,56 lim-
ited access to spirometry57 or lack of belief that a
guideline or checklist will produce positive outcomes.10,49
Other HCPs viewed guidelines as inflexible15 or identified
that asthma guidelines do not thoroughly focus on severe
asthma.10 Moreover, external barriers influencing HCPs’
adherence to guidelines include lack of time,51 organiza-
tional constraints10 and inability to reconcile patient pre-
ferences with guideline recommendations.52 Several
approaches have been undertaken to address these issues
in severe asthma. GINA published practical recommenda-
tions about how to identify, assess and manage difficult to
treat and severe asthma in adolescent and adult patients.1
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Practice guidelines are designed to provide recommenda-
tions to assist and guide HCPs in making clinical
decisions.58 When used by an HCP in practice, asthma
guidelines could minimize diagnosis and assessment
inconsistencies, reducing avoidable emergency department
visits and hospitalizations.58 Furthermore, to overcome the
barriers related to the lack of training and resources avail-
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able for severe asthma clinicians, the Australian Centre of
Excellence in Severe Asthma produced an online toolkit to
provide evidence-based guidance to clinicians globally
(http://toolkit.severeasthma.org.au). The main goal of pro-
viding the toolkit is to equip HCPs with clinical resources
essential in the management of severe asthma.59 Thus,
better meeting the needs of HCPs across health care set-
tings irrespective of geographical locations.59 The Severe
Asthma Toolkit offers the latest treatment options to opti-
mize care in severe asthma patients, covering various
modules ranging from medications, diagnosis, assessment,
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management and comorbidities among others.59 The
toolkit was created by a world-class multidisciplinary
team with clinical expertise in severe asthma.59
Inconsistent approach for diagnosis or management
Despite the significance of spirometry in respiratory func-
tion testing for assessing severity, the test is widely under-
utilized for asthma in primary care.32 Furthermore,
biomarkes used in severe asthma management are also
underutilized, in an online survey to clinicians involved
in severe asthma management, 53% of the respondents
indicated that they never used FeNO testing,10 a surrogate
marker of eosinophilic airway inflammation.
Similarly, this survey also reported that assessments for
some comorbidities such as naso-endoscopy, functional
exercise test or bone mineral densitometry were never
initiated, by 60%, 46% and 32% of the respondents,
respectively.10 Health status, asthma control and comor-
bidities questionnaires were also inconsistently used.10 Of
note, determining whether or not a treatment effect is
clinically meaningful is a great challenge in severe
asthma.60 Barriers to routine use of self-reported
questionnaires include logistical, technical and lengthy
administration inhibiting successful adoption of some
patient-reported outcome measures (PROMs) in clinical
practice.2 PROMs that have been developed specifically
for severe asthma provide a valid assessment of the
patient’s health status, level of control and experience of
severe asthma and are useful in the clinic.2 Variability in
diagnosis, assessment and management could lead to
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Majellano et al
serious consequences for patients with severe asthma.15
Diagnostic uncertainty in asthma still exists, with severe
asthma being underdiagnosed or overdiagnosed,61 indicat-
ing that diagnostic precision remains a serious issue in the
era of targeted therapy.
Referral pathways
Referral systems offer patients access to expert HCPs in
the field of severe asthma.32,52 A timely referral to specia-
lized care should be actioned when patients in primary
health care continue to experience suboptimal control,
with increased severity, despite guideline-based
treatment.62 Notwithstanding the importance of a linkage
pathway, variations in referral patterns from primary
health care to secondary health care have been a constant
concern both at the international48 and national scene.10
The lack of clear referral criteria limits success in optimal
management. McDonald et al10 highlighted that for a
referral system to work in severe asthma, a referral at all
levels of care should be defined. One example of a referral
intervention from primary health care to secondary health
care is the SIMPLES model.63 The SIMPLES model is a
structured framework used in primary health care to eval-
uate patients with difficult to control asthma.62,63 If
patients have not achieved control despite structured
reviews, a referral to severe asthma specialist clinic is
warranted for further evaluation and management.62 The
SIMPLES approach suggests a good interface between
primary and specialist care, integrating clinical assessment
and management, whilst avoiding inappropriate escalation
of treatments.62,63
Orozco-Beltran et al48 conducted a study using a mod-
ified Delphi method on the management and referral of
severe and poorly controlled asthma where they found
physicians dissatisfaction in the referral process. The
majority of non-severe asthma patients are treated in sec-
ondary health care when they can be appropriately mana-
ged in primary health care.48 The lack of clarity and
consensus of the referral criteria between primary health
care and secondary health care drives up costs and diver-
sion of resources.48 A retrospective observational study64
has also reported findings that are consistent with the out-
comes of Beltran et al.48 HCPs have identified the need for
a well-defined and extensive criteria to guide referral
decision making and to ensure equitable access to avail-
able health services.10,48
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 Majellano et al
Barriers related to patients and
clinicians
A number of factors have been identified as contributing to
suboptimal severe asthma assessment: patient–provider
communication, personal perceptions or beliefs65 and
managing symptoms and risk factors.60
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Poor patient–physician communication
Effective patient–provider relationships are important for
patients with asthma and can lead to improved outcomes.66
Communication is a cardinal component and foundation
for a positive patient–provider relationship, increasing
patient satisfaction and better adherence to treatment.66
As a result, satisfied patients are more likely to share
critical health information with their physicians.66
However, conflicting perception between the patient
and the HCP can negatively impact patients’ health.67
For personal use only.
The observational study of discordance in patients and
HCPs’ views on asthma control by Crespo-Lessmann
et al67 concluded that patient–provider discordance is
likely to contribute to an increased risk of poor asthma
control. Communication is a fundamental element to
developing a patient-centered treatment plan but authori-
tarianism or paternalism in clinical settings disempowers
patients, limiting a two-way conversation.68 The level of
respect, time constraint, cultural and language diversity
also impede stronger relationships and communication
between patients and physicians.69
Patient personal perceptions
The patient’s perspective is essential to both assessment
and management of severe asthma, but when patients
overestimate or underestimate disease severity or the
level of asthma control required, then it becomes a sig-
nificant barrier.70 A qualitative study by Bidad et al71 that
sought to determine patients’ perception of asthma control
identified five themes: (a) personal meaning of control, (b)
intermittent prevention, (c) compromising control to avoid
medication, (d) pharmacological agents overemphasized in
control and (e) the role of asthma review in control.71 In
one of the themes, patients described having their own
“internal barometer” of the level of symptoms in determin-
ing when their level of control was decreasing and this was
determined to be much higher than the asthma control test
(ACT) cut points.71 Moreover, primary care patients did
not perceive asthma review appointments as an advantage
to asthma control, but rather as an additional burden.71
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This perception was compounded by clinical practice var-
iations and conflicting advice provided by HCPs.71
Managing symptoms and risk factors
The complexity of severe asthma explains why patients
seek a comprehensive understanding about their disease.60
When patients acquire greater understanding of their illness,
a sense of control and empowerment is achieved enabling
them to make positive choices and set goals.68
Unfortunately, the patients’ journey toward acquiring the
desired knowledge is not straightforward. When faced with
ambiguity, patients have reported that they receive little
information from their HCPs.68 As a result, patients will
seek information from elsewhere, including potentially
unreliable sources.68 Individuals with limited knowledge
about asthma symptoms, common triggers and risk factors
are at a heightened risk for poor asthma control. Limited
health literacy in patients and an absence of patient-centered
care can lead to non-adherence to medications and subopti-
mal self-management.68 In an explorative study by Lingner
et al72 on patient and HCPs’ concept of good asthma treat-
ment, patients desired to share the decision-making process
with their HCPs. However, several patients discussed their
reluctance to discuss their asthma with their HCP due to
their perception that their HCPs had preconceived notions,
for example, “they always blame your weight”,68 implicat-
ing a barrier to the patient–clinician relationship.60
Barriers related to system factors
and equitable access to specialized
service
There are numerous factors influencing delivery of care.
Barriers arising from the structural level include longer
waiting lists due to lack of specially trained HCPs, high
service demand32 coupled with insufficient resources.10 In
addition, there is a complex procedure required to access
novel therapies12 and there is limited access to some
biomarkers in many facilities.73
Geographic barriers disproportionately burden patients
with financial incapacities or even severe asthma patients
who require closer attention from the specialist and multi-
disciplinary team (MDT).10 MDTs are a group of HCPs
who coordinate, manage and organize care for people with
severe asthma.31 The core staff necessary to run a severe
asthma clinic includes respiratory physician, specialist
nurse, pulmonary function scientist and speech
pathologist.31
Journal of Asthma and Allergy 2019:12
 Dovepress
Often rural patients have to travel long distances to
specialized services and therefore, places severe asthma
patients in a difficult position, weighing up travel costs and
benefits.10
Waitlist and appointment delays
Longer waiting times suggest underlying issues or unre-
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solved conflicts in resources, stakeholders, policies or sys-
tems in the delivery of services.74 This means that
prolonged waiting periods are significant barriers for
patients. Not being able to obtain the right services and
appropriate treatments at the right time impacts patient
expectations and satisfactions.75 Some studies have
demonstrated that appointment delay causes stress for
both patients and HCPs reducing positive outcomes.74
Fielden et al76 demonstrated that prolonged waiting times
of >6 months result in greater economic costs and dete-
rioration in physical function and in HRQoL.
For personal use only.
Complexities of accessing novel biological
therapies
With the use of novel biological therapies on the rise,
patients deserve timely access to these targeted
treatments.62 Access to novel therapies can vary signifi-
cantly across international health care settings and requires
different prerequisites before these drugs can be pre-
scribed. In Australia, the long waiting periods of usually
6–12 months deter access to biologics.10,12 During those
months, specialists, for their part, are trying one or more
add-on therapies before initiating biological therapies.12
Lack of accessible biomarkers
In order to improve outcomes for severe asthma patients, it
is critical that we devise a more definitive approach to
assessing patients with asthma. Biomarkers represent a
solution to characterizing patients in order to predict prog-
nosis and treatment response.77 Airway inflammation is an
acceptable starting point for discovering biomarkers as
inflammation plays a critical role in underlying
pathologies.78–80 The current gold standard of assessing
airway inflammation is sputum cell counts but this has
limitations in the clinical setting. Techniques involved in
collecting and processing specimens are time-consuming,
require skill and there are issues with reproducibility and
inconsistent cut-off values, restricting sputum cell count-
ing to specialized- or research-based centers.81 In
response, surrogates of airway inflammation have been
Journal of Asthma and Allergy 2019:12
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Majellano et al
developed, including blood eosinophils,82 FeNO83,84 and
periostin.85 However, none are free from contradicting
results81,86,87 and confounding factors.88,89 As a result,
the use of these markers in diagnosis and assessment,
prediction and prognosis has had slow uptake but is a
priority for future research and current practice. In addi-
tion, although biomarkers indicative of eosinophilic
inflammation have been developed and validated, there
are currently no biomarker surrogates for non-eosinophilic
inflammation.90,91 This is of critical importance as many
severe asthma patients present with non-eosinophilic
inflammation and some may have persistent neutrophilic
inflammation.92
So how do we develop the “ideal biomarker”? Many
factors determine the ideal biomarker and can act as hin-
drances to biomarker development and its clinical utility.93
Important in the clinical setting are that biomarkers are
accessible and non-invasive and the techniques to measure
are rapid, straightforward and relatively inexpensive.93
Whereas, it is completely valid to use invasive techniques,
such as bronchial biopsies and bronchial lavage, to detect
new molecular pathways and mechanisms, accessible bio-
marker sources such as blood, urine, sputum and exhaled
breath are preferred. Additionally, due to the complexity of
asthma, a single biomarker will not be sufficient to capture
the full disease process. Therefore, we need further
research generating composite panels of biomarkers from
varying non-invasive sources.73,94
Commendations must be made to the surrogate inflam-
matory biomarkers that do exist. But unfortunately, bio-
markers must also be reliable and reproducible and despite
the great amount of research that has been invested in
biomarker discovery and testing, the ideal biomarker
does not yet exist in asthma and conflicting results and
limitations still remain a reality.
Overcoming barriers
To facilitate optimal evaluation and assessment of severe
asthma, the following key recommendations should be
taken into consideration.
Strategies related to health professional
factors
Optimization of referral avenues and guidelines
A centralized web-based database system can facilitate the
transmission of valuable information.10 When necessary,
treating physicians have the capacity to access details
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 Majellano et al
including asthma symptom severity, exacerbation fre-
quency, past and current therapies and spirometry
outcomes.32 The accessibility of this information can
shorten the patients’ journey through the referral path-
ways, which can lead to improved HRQoL for severe
asthma patients.62 In addition, establishing a universal
referral pathway to help select patients who will likely
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benefit from specialist evaluation can also streamline
care.10,13 To reinforce suitable referrals, regular monitor-
ing should be implemented especially to patients with
moderate or severe asthma.95 For example, pulmonary
specialists should follow-up patients admitted with severe
asthma exacerbations for at least 1 year after the
admission.52
Provision for telehealth consultations from primary
health care to secondary health care strengthens referral
pathway as well.48 It should be noted that primary care
For personal use only.
implements a gatekeeping system, whereby the general
practitioner (GP) is in the principal position to recognize
poorly controlled asthma.32 The need to establish and
develop a mechanism for involving GPs in the manage-
ment of asthma should be consistent from the assessment
all the way to the administration of biological therapies.32
Systems in which patients can have their novel biological
therapies administered within primary care, similar to
rheumatoid arthritis, have been proposed to substantially
reduce the burden of specialists in asthma services, paving
the way to conveniently accommodate more patients.10,32
Use of assessment tools
The use of assessment tools, specifically subjective and
objective tools in severe asthma assists in viewing patients
from a multidimensional perspective.9 Furthermore, out-
comes from the assessment form the basis of the care plan.
The Centre of Excellence in Severe Asthma has developed
valuable resources for HCPs, packaged in an online toolkit
https://toolkit.severeasthma.org.au/.96 The Severe Asthma
Toolkit is comprehensive and provides a convenient, easy-
to-use resource to support and equip clinicians on how to
achieve optimal severe asthma management.96
Furthermore, to enhance diagnostic and assessments pro-
ficiency, knowledge dissemination within the workplace
either through video conferencing, seminars and webinars
can aid in practice.97 Decision support tools like compu-
terized systems, treatment guides, and standardized pre-
scriptions assist HCPs in treatment decision making.97
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Strategies related to patient factors
Patient–physician communication
The patient–provider relationship is dependent on good
communication skills.66 Apart from clinical competence,
HCPs are required to master and demonstrate empathy,
compassion, caring, non-judgment, open and concern dur-
ing patient encounters.68 There is a wealth of evidence in
the literature that supports the benefit of efficient and
effective communication resulting in increased patient
satisfaction, better health outcomes, and decreased health
care utilization98 even without lengthening appointment
times.99 Providing a patient-centered care (PCC) approach
is essential in asthma management. Under a PCC model,
partnerships in health between HCPs, patients and carers
are highlighted.100 Consideration of patients’ preferences
and values is demonstrated through patients’ active parti-
cipation in clinical decision making.100 A PCC model acts
as a springboard in promoting flexible provision of health
care and is moving beyond the traditional paternalistic
approach.100 Additionally, the role of patient advocates
help patients navigate the health care system and bridge
between patient and their treating clinicians reducing com-
munication gaps.101 Furthermore, communication failures
between HCPs can be fostered through regular meetings
and joint clinical sessions.48
Strategies related to organizational
factors
Assuring appropriate resourcing
The severe asthma health workforce depends on the size of
the service. In a conservative setting, at least one pulmon-
ary physician and nurse specialist are needed; a second
physician is necessary to overcome patient load or
absences.31 When workforce shortages exist, partnerships
with nearby asthma network services may mitigate short-
term periods of absence.13 Benefits of a shared-care
model, wherein special arrangements between public and
private providers offer opportunity for expanding services
and resources.13,102
Improve access to MDT
Specialist MDTs are core for confirming diagnosis of
severe asthma.13 To optimize phenotyping and targeted
therapy, providing continuous education and trainings for
MDT members in severe asthma management is
warranted.10 Onsite availability and participation of
Journal of Asthma and Allergy 2019:12
 Dovepress
nursing and allied health offer efficient services.13 Funding
for MDT could be achieved through a clinical re-design
approach.31 This method seeks to balance the costs and
benefits, by reducing health care utilization and justifying
the utilization of expensive therapies and patient out-
comes. The use of teleconferencing or video-linked MDT
discussion to its full advantage allows other practitioners
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to collaborate in decision-making process.13 Telehealth
can break down the wall of geographical barriers for
patient treatment, follow up or initial in-person
consultation.10,13
Accessible biomarkers
A two-step approach can be taken to develop strategies to
overcome barriers obstructing biomarker development and
use in primary care. The first step is to discover novel
biomarkers. Followed by the investigation and validation
of newly discovered biomarkers from non-invasive
For personal use only.
sources, using easy-to-measure techniques.
“Omics” technology epitomizes the advancements that
have been made in medicine and science. This new gen-
eration of exploratory science refers to the study of the
biological system. They include, but are not limited to,
genomics, proteomics, transcriptomics and metabolomics.
The use of computational networking, bioinformatics and
systems biology seeks to interpret the “big data” generated
from the extensive exploration of the human organism.103,104
In asthma, unbiased “omics” screening studies have been
used to discover novel biomarkers, such as protein measure-
ments in proteomics studies105 and differential gene expres-
sion in transcriptomic studies.106 With methods used to
obtain data becoming less expensive and databases becoming
larger and more secure to store the deluge of data, “omics”
studies are becoming more prevalent and the combination of
“omics” data, known as “multiomics”, is expanding,107 dee-
pening our understanding of the molecular and genetic path-
ways underlying disease.
In tying in with the characteristics of the “ideal bio-
marker”, new biomarkers must also be easy to obtain from
non-invasive sources, using feasible techniques.
Biomarkers from easily accessible tissues and fluids such
as blood, urine, sputum and exhaled breath are ideal.
Serum provides one of the most ideal sources for biomar-
kers as blood collection, serum preparation and analysis
are highly standardized techniques and collection is mini-
mally invasive.73 However, recent studies in asthma have
found that urine73 and exhaled breath88 are also promising
sources of novel biomarkers, especially for children.108
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Majellano et al
Although, these will require further research to validate.
An example of ongoing research into non-invasive alter-
natives to sputum induction and more feasible measure-
ments of airway biomarkers are through the recently
developed absorptive nasal strip technology. Technology
within absorptive strips permits the sampling of mucosal
fluid within the upper respiratory tract109 and measurement
of airway inflammatory biomarkers, successfully shown to
reflect sputum eosinophilia in a recent small study in
asthma.110 As a result, the powerful use of new technolo-
gies that convert ongoing advances of biomedical research
into user-friendly tools that supplements and enhances
current clinical tools can facilitate inter-professional com-
munication between basic scientists, medical researchers
and clinicians.111
Point-of-care testing will also allow for fast and on-site
assessment of multiple biomarkers.112 In addition to bio-
sensors and wearable monitoring devices, technology that
continuously measures analytes in body fluids are cur-
rently being developed that could give real-time data on
the measurement of specific molecules or biomarkers.113
These point-of-care tests empower clinicians and allow
patients to participate in the clinical decision-making pro-
cess; an enabler for patient–clinician dialogue regarding
treatment and management options.
Conclusion
Barriers to severe asthma assessment are influenced by
multiple factors and can be grouped according to HCP-,
patient- and systems-related factors. We have identified the
barriers to assessing severe asthma and presented strate-
gies to overcome these barriers. The highlighted barriers
relate to inconsistent approaches to diagnosis and assess-
ment, under referral, gaps in communication, poor percep-
tion on asthma control and organizational delimitations.
Facilitators to overcome barriers to severe asthma assess-
ment are standardized approaches and referrals, use of
assessment tools and guidelines, implementation of a
patient-centered care approach and better resources.
Important opportunities of utilizing multidimensional
assessment as an approach for implementation of care
needs to be pursued where possible, to help overcome
barriers in the assessment of severe asthma.
Multidimensional assessment requires systematic assess-
ment across three key domains (pulmonary/airway, extra-
pulmonary/comorbidity and risk factor/behavioral
domains) and can help identify important and clinically
relevant traits, and help guide treatment decisions.
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 Majellano et al
Recognizing that multidimensional assessment can be time
consuming and requires specialist teams, we propose that
the benefits of this approach outweigh these barriers. This
review highlights the need for further research into deter-
mining HCPs’ views of a feasible and acceptable approach
to implement effective severe asthma management and
generating composite panels of biomarkers from various
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non-invasive resources. These barriers are worthy of our
attention if we desire a precision assessment in severe
asthma.
Abbreviations
AHR, airway hyper-responsiveness; ICS, inhaled corticos-
teroids; GINA, Global Initiative for Asthma; LABA, long-
acting beta agonist; IgE, immunoglobulin-E; FeNO,
exhaled fraction of nitric oxide; ACQ, Asthma Control
Questionnaire; ACT, asthma control test; FEV1, forced
expiratory volume in one second; FVA, forced vital capa-
For personal use only.
city; RCT, randomized controlled trial; HCP, health care
professional; MDT, multidisciplinary team; GP, general
practitioner; PCC, patient-centered care; HRQoL, health-
related quality of life; PROMs, patient-reported outcome
measures.
Disclosure
Dr Vanessa L Clark reports personal fees from Astra
Zeneca and grants from National Health and Medical
Research Council, outside the submitted work. Professor
Peter G Gibson reports grants and personal fees from
AstraZeneca, GlaxoSmithKline, Sanofi and Novartis, out-
side the submitted work. Professor Vanessa McDonald
reports grants and personal fees from AstraZeneca, GSK
and personal fees from Menarini, outside the submitted
work. The authors report no other conflicts of interest in
this work.
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